The neuropeptide oxytocin (OXT) is a crucial mediator of parturition and milk ejection and a major modulator of various social behaviors, including social recognition, aggression and parenting. In the past decade, there has been significant excitement around the possible use of OXT to treat behavioral deficits in neurodevelopmental disorders, including autism spectrum disorder (ASD). Yet, despite the fast move to clinical trials with OXT, little attention has been paid to the possibility that the OXT system in the brain is perturbed in these disorders and to what extent such perturbations may contribute to social behavior deficits. Large-scale whole-exome sequencing studies in subjects with ASD, along with biochemical and electrophysiological studies in animal models of the disorder, indicate several risk genes that play an essential role in brain synapses, suggesting that deficits in synaptic activity and plasticity underlie the pathophysiology in a considerable portion of these cases. OXT has been repeatedly shown, both in vitro and in vivo, to modify synaptic properties and plasticity and to modulate neural activity in circuits that regulate social behavior. Together, these findings led us to hypothesize that failure of the OXT system during early development, as a direct or indirect consequence of genetic mutations, may impact social behavior by altering synaptic activity and plasticity. In this article, we review the evidence that support our hypothesis.
Bibliographical noteFunding Information:
Funding. The Seaver Foundation, The Ministry of Science, Technology and Space of Israel (Grant #3-12068), Chica and Heinz Schaller Research Foundation, Deutsche Forschungsgemeinschaft (DFG) within the Collaborative Research Center (SFB) 1134 and 1158, SNSF-DFG grant GR 3619/8-1, ANR-DFG grant GR 3619/7-1, Fritz Thyssen Research grant 10.16.2.018MN and Human Frontier Science Program grant RGP0019/2015, National Institute of Mental Health R01-MH101584.
© Copyright © 2018 Thirtamara Rajamani, Wagner, Grinevich and Harony-Nicolas.
- animal models for ASD
- autism spectrum disorder (ASD)
- neurodevelopmental disorder
- synaptic plasticity
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Cell Biology